RV infection during first trimester of pregnancy can result in congenital abnormalities . These abnormalities are thought to be due to the cellular growth retardation induced by RV infection. Further, it has also been observed that about 25% of adult women vaccinees develop persistent RV infection which leads to chronic arthritis. We have observed host proteins, that are autoantigens, are necessary for RV replication. We have characterized some of these host proteins and discovered that they play a role in cell cycle control. One of the host proteins is a homologue of human calreticulin which is a phosphoprotein and the phosphorylation is necessary for its interaction with RV RNA during replication. The phosphorylation of calreticulin is cell cycle regulated and is accellerated upon RV infection. Therefore understanding the interaction between the calreticulin and viral replication components and the effect of such interaction on the cell growth could provide insight in RV induced teratogenesis and the mechanism of RV vaccine induced persistent infection in adult women. The project addresses the issue of live-virus vaccine safety. Further, the research dealing with the pathogenesis of RV vaccine virus will provide understanding of live-virus vaccine related adverse reactions. It also enables the agency to provide guidance to manufacturers of viral vaccines with regards to safety and efficicacy. In addition,the outcome of this research is resulting in the development of standards for manufacturing of products using viral vectors. Studying RV induced cell growth alteration provides an excellant regulatory knowhow about other live-virus childhood vaccines and the cause of their adverse reactions. Research done with RV can thus provide impetus in the development of policy for efficient and less cumbersome regulatory process for live-viral as well as recombinant vaccines. It also allows us to review the mechanism of antiviral drugs being developed against new viruses.